Purpose: To identify factors associated with crestal bone gain around single-tooth implants. Materials and Methods: A retrospective cohort study was conducted. More than 90 different local and systemic factors were documented. Descriptive statistics and univariate and multivariate mixed-effects regression models, adjusted for multiple implants in the same patient, were used to identify predictors of crestal bone gain after insertion of definitive restorations. Results: Eighty-one subjects who received 326 Bicon implants were followed for an average of 70.7 months. Eighty-one implants in 46 patients showed varying degrees of apparent bone gain over time. Variables associated with peri-implant bone gain in the first multivariate model were: type of opposing structure, tooth (P = .02); type of restoration, crown cemented on a prefabricated titanium abutment with a spherical base (P = .006); hydroxyapatite coating (P = .0005); implant size 5 × 8 mm (P = .02); and daily intake of nonsteroidal anti-inflammatory drugs (NSAIDs) (P =.04). NSAIDs remained significantly correlated to crestal bone gain in the second multivariate analysis; an implant was significantly more likely to gain bone if the patient was taking NSAIDs daily (P = .02), but this effect was specific to hydroxyapatite-coated implants (P = .01). Conclusion: Daily doses of NSAIDs were correlated with a significant increase in crestal bone levels around single-tooth hydroxyapatite-coated implants following crown insertion. Keywords: dental implants, nonsteroidal anti-inflammatory drugs, peri-implant bone gain, prospective cohort study, risk factors